19-44751358-C-G

Variant names:

• chr19-44751358-C-G
• NM_005178.5:c.388C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005178.5(BCL3):​c.388C>G​(p.Arg130Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BCL3 NM_005178.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

Genes affected

BCL3 (HGNC:998): (BCL3 transcription coactivator) This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha-locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin repeats, which are most closely related to those found in I kappa B proteins. This protein functions as a transcriptional co-activator that activates through its association with NF-kappa B homodimers. The expression of this gene can be induced by NF-kappa B, which forms a part of the autoregulatory loop that controls the nuclear residence of p50 NF-kappa B. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2246033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL3	NM_005178.5	c.388C>G	p.Arg130Gly	missense_variant	Exon 2 of 9	ENST00000164227.10	NP_005169.2
BCL3	XM_011527198.4	c.388C>G	p.Arg130Gly	missense_variant	Exon 2 of 9		XP_011525500.3
BCL3	XM_017027110.2	c.268C>G	p.Arg90Gly	missense_variant	Exon 2 of 7		XP_016882599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL3	ENST00000164227.10	c.388C>G	p.Arg130Gly	missense_variant	Exon 2 of 9	1	NM_005178.5	ENSP00000164227.5
BCL3	ENST00000444487.1	c.37C>G	p.Arg13Gly	missense_variant	Exon 1 of 8	5		ENSP00000393731.1
BCL3	ENST00000403534.7	n.556C>G		non_coding_transcript_exon_variant	Exon 2 of 8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445876 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719616

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.050
Sift	Benign	0.038	D
Sift4G	Benign	0.093	T
Polyphen		0.32	B
Vest4		0.52
MutPred		0.41		Loss of loop (P = 9e-04);
MVP		0.57
MPC		0.31
ClinPred		0.22	T
GERP RS		2.9
Varity_R		0.14
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-45254615;